title: Inhibition of human sperm motility by contraceptive anti-eppin antibodies from infertile male monkeys: effect on cyclic adenosine monophosphate.
abstract: Epididymal protease inhibitor (eppin [official symbol, SPINLW1]) is of interest as a male contraceptive target because of its specificity and location on the human sperm surface. We have examined the effect of anti-eppin antibodies from infertile male monkeys and the effect of recombinant human semenogelin on human sperm motility. Anti-eppin antibodies significantly decreased the progressive motility of human spermatozoa as measured by decreased total distance traveled, decreased straight-line distance, and decreased velocity. Anti-eppin treatment of spermatozoa significantly increased the amount of cAMP present in nonprogressive spermatozoa; however, approximately 25% of antibody-treated spermatozoa could be rescued by the addition of cAMP-acetoxymethyl ester, indicating that anti-eppin-treated spermatozoa have a compromised ability to utilize cAMP. Addition of recombinant human semenogelin has a concentration-dependent inhibitory effect on progressive motility (increased tortuosity and decreased velocity). We tested the hypothesis that anti-eppin antibodies bound to eppin would subsequently block semenogelin binding to eppin. Anti-eppin antibodies from infertile monkeys inhibited eppin from binding to semenogelin. Addition of affinity-purified antibodies made to the dominant C-terminal epitope of eppin had an inhibitory effect on progressive motility (increased tortuosity, decreased velocity, and straight distance). Our results suggest that the eppin-semenogelin binding site is critical for the removal of semenogelin in vivo during semen liquefaction and for the initiation of progressive motility. We conclude that the eppin-semenogelin binding site on the surface of human spermatozoa is an ideal target for a nonsteroidal male contraceptive.
authors.affiliation: Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. morand@unc.edu
authors.forename: Michael G
authors.initials: MG
authors.lastname: O'Rand
authors.forename: Esther E
authors.initials: EE
authors.lastname: Widgren
authors.forename: Stan
authors.initials: S
authors.lastname: Beyler
authors.forename: Richard T
authors.initials: RT
authors.lastname: Richardson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D000882:Haplorhini / Q000276:immunology; D006801:Humans; D007248:Infertility, Male / Q000276:immunology*; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D053491:Proteinase Inhibitory Proteins, Secretory / Q000276:immunology* / Q000378:metabolism; D029607:Seminal Vesicle Secretory Proteins / Q000378:metabolism; D013081:Sperm Motility / Q000187:drug effects* / Q000276:immunology
chemical_list: D000906:Antibodies; D003272:Contraceptive Agents, Male; C431553:Eppin protein, human; D053491:Proteinase Inhibitory Proteins, Secretory; D029607:Seminal Vesicle Secretory Proteins; C424482:seminal vesicle-specific antigen; D000242:Cyclic AMP